Immune Cells in Cancer Therapy and Drug Delivery

Figure 1

Wnt signaling and macrophages. Wnt signaling pathway is one of the most important pathways regulating cells proliferation, differentiation, polarity, and migration. At least two distinct pathways transduce Wnt signals: canonical Wnt/β-catenin pathway and the β-catenin independent noncanonical Wnt pathway (Wnt/Ca²⁺ signaling and Wnt/planar cell polarity (PCP) signaling). Wnt/β-catenin signaling pathway is upregulated in many cancers. Lack of β-catenin degradation and its nuclear accumulation is an evidence of activated Wnt/β-catenin pathway. β-catenin acts in the nucleus as a transcription factor increasing cancer proliferation and survival. Activation of Wnt/PCP signaling during development results in cytoskeleton remodeling (by Rho, Ras, and JNK) promoting cell movement. Calcium dependent Wnt increases the motility of various cell types by regulating the formation of lamellipodia. It also increases expression of vimentin and therefore induces an epithelial-mesenchymal transition, the crucial step in metastasis. Macrophages infiltrated to tumour mass inhibit cell proliferation as effect of inhibition of Wnt/β-catenin pathway. However canonical and noncanonical Wnt pathways work on the principle of antagonism, so macrophages inhibiting β-catenin pathway activate noncanonical Wnt pathway and lead to cytoskeleton remodeling in cancer cells and facilitate their motility.